Viral Infections of the Skin Part 2 (Genital Herpes and Warts) *

Transcription

1 OpenStax-CNX module: m Viral Infections of the Skin Part 2 (Genital Herpes and Warts) * Geo Lin-Cereghino Based on Viral Infections of the Reproductive System by OpenStax This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License 4.0 Several viruses can cause serious problems for the human reproductive system. Most of these viral infections are incurable, increasing the risk of persistent sexual transmission. In addition, such viral infections are very common in the United States. For example, human papillomavirus (HPV) is the most common STI in the country, with an estimated prevalence of 79.1 million infections in 2008; herpes simplex virus 2 (HSV-2) is the next most prevalent STI at 24.1 million infections. 1 In this section, we will examine these and other major viral infections of the reproductive system. 1 Genital Herpes Genital herpes is a common condition caused by the herpes simplex virus (Figure 1), an enveloped, double-stranded DNA virus that is classied into two distinct types. Herpes simplex virus has several virulence factors, including infected cell protein (ICP) 34.5, which helps in replication and inhibits the maturation of dendritic cells as a mechanism of avoiding elimination by the immune system. In addition, surface glycoproteins on the viral envelope promote the coating of herpes simplex virus with antibodies and complement factors, allowing the virus to appear as self and prevent immune system activation and elimination. There are two herpes simplex virus types. While herpes simplex virus type 1 (HSV-1) is generally associated with oral lesions like cold sores or fever blisters (see Viral Infections of the Skin and Eyes), herpes simplex virus type 2 (HSV-2) is usually associated with genital herpes. However, both viruses can infect either location as well as other parts of the body. Oral-genital contact can spread either virus from the mouth to the genital region or vice versa. * Version 1.1: Aug 19, :03 pm Catherine Lindsey Satterwhite, Elizabeth Torrone, Elissa Meites, Eileen F. Dunne, Reena Mahajan, M. Cheryl Bañez Ocfemia, John Su, Fujie Xu, and Hillard Weinstock. Sexually Transmitted Infections Among US Women and Men: Prevalence and Incidence Estimates, Sexually Transmitted Diseases 40, no. 3 (2013):

2 OpenStax-CNX module: m Figure 1: Virions of the herpes simplex virus are shown here in this transmission electron micrograph. (credit: modication of work by Centers for Disease Control and Prevention) Many infected individuals do not develop symptoms, and thus do not realize that they carry the virus. However, in some infected individuals, fever, chills, malaise, swollen lymph nodes, and pain precede the development of uid-lled vesicles that may be irritating and uncomfortable. When these vesicles burst, they release infectious uid and allow transmission of HSV. In addition, open herpes lesions can increase the risk of spreading or acquiring HIV. In men, the herpes lesions typically develop on the penis and may be accompanied by a watery discharge. In women, the vesicles develop most commonly on the vulva, but may also develop on the vagina or cervix (Figure 2). The symptoms are typically mild, although the lesions may be irritating or accompanied by urinary discomfort. Use of condoms may not always be an eective means of preventing transmission of genital herpes since the lesions can occur on areas other than the genitals.

3 OpenStax-CNX module: m Figure 2: Genital herpes is typically characterized by lesions on the genitals (left), but lesions can also appear elsewhere on the skin or mucous membranes (right). The lesions can be large and painful or small and easily overlooked. (credit b: modi cation of work by Schi er JT, Swan D, Al Sallaq R, Magaret A, Johnston C, Mark KE, Selke S, Ocbamichael N, Kuntz S, Zhu J, Robinson B, Huang ML, Jerome KR, Wald A, and Corey) Herpes simplex viruses can cause recurrent infections because the virus can become latent and then be 2 reactivated. This occurs more commonly with HSV-2 than with HSV-1. The virus moves down peripheral nerves, typically sensory neurons, to ganglia in the spine (either the trigeminal ganglion or the lumbar-sacral ganglia) and becomes latent. Reactivation can later occur, causing the formation of new vesicles. HSV-2 most e ectively reactivates from the lumbar-sacral ganglia. Not everyone infected with HSV-2 experiences reactivations, which are typically associated with stressful conditions, and the frequency of reactivation varies throughout life and among individuals. Between outbreaks or when there are no obvious vesicles, the virus can still be transmitted. Virologic and serologic techniques are used for diagnosis. The virus may be cultured from lesions. The immunostaining methods that are used to detect virus from cultures generally require less expertise than methods based on cytopathic e ect (CPE), as well as being a less expensive option. However, PCR or other DNA ampli cation methods may be preferred because they provide the most rapid results without waiting for culture ampli cation. PCR is also best for detecting systemic infections. Serologic techniques are also useful in some circumstances, such as when symptoms persist but PCR testing is negative. While there is no cure or vaccine for HSV-2 infections, antiviral medications are available that manage the infection by keeping the virus in its dormant or latent phase, reducing signs and symptoms. If the medication is discontinued, then the condition returns to its original severity. The recommended medications, which may be taken at the start of an outbreak or daily as a method of prophylaxis, are and valacyclovir. acyclovir, famciclovir, 1.1 Neonatal Herpes Herpes infections in newborns, referred to as neonatal herpes, are generally transmitted from the mother to the neonate during childbirth, when the child is exposed to pathogens in the birth canal. Infections can occur regardless of whether lesions are present in the birth canal. In most cases, the infection of the newborn is limited to skin, mucous membranes, and eyes, and outcomes are good. However, sometimes the 2 Centers for Disease Control and Prevention Sexually Transmitted Disease Treatment Guidelines: Genital Herpes,

4 OpenStax-CNX module: m virus becomes disseminated and spreads to the central nervous system, resulting in motor function decits or death. 2 Human Papillomas Warts of all types are caused by a variety of strains of human papillomavirus (HPV) (see Viral Infections of the Skin and Eyes). Condylomata acuminata, more commonly called genital warts or venereal warts (Figure 3), are an extremely prevalent STI caused by certain strains of HPV. Condylomata are irregular, soft, pink growths that are found on external genitalia or the anus. HPV is a small, non-enveloped virus with a circular double-stranded DNA genome. Researchers have identied over 200 dierent strains (called types) of HPV, with approximately 40 causing STIs. While some types of HPV cause genital warts, HPV infection is often asymptomatic and self-limiting. However, genital HPV infection often co-occurs with other STIs like syphilis or gonorrhea. Additionally, some forms of HPV (not the same ones associated with genital warts) are associated with cervical cancers. At least 14 oncogenic (cancer-causing) HPV types are known to have a causal association with cervical cancers. Examples of oncogenic HPV are types 16 and 18, which are associated with 70% of cervical cancers. 3 Oncogenic HPV types can also cause oropharyngeal cancer, anal cancer, vaginal cancer, vulvar cancer, and penile cancer. Most of these cancers are caused by HPV type 16. HPV virulence factors include proteins (E6 and E7) that are capable of inactivating tumor suppressor proteins, leading to uncontrolled cell division and the development of cancer. HPV cannot be cultured, so molecular tests are the primary method used to detect HPV. While routine HPV screening is not recommended for men, it is included in guidelines for women. An initial screening for HPV at age 30, conducted at the same time as a Pap test, is recommended. If the tests are negative, then further HPV testing is recommended every ve years. More frequent testing may be needed in some cases. The protocols used to collect, transport, and store samples vary based on both the type of HPV testing and the purpose of the testing. This should be determined in individual cases in consultation with the laboratory that will perform the testing. 3 Lauren Thaxton and Alan G. Waxman. Cervical Cancer Prevention: Immunization and Screening Medical Clinics of North America 99, no. 3 (2015):

5 OpenStax-CNX module: m64856 Figure 3: Genital warts may occur around the anus (left) or genitalia (right). (credit left, right: modi cation of work by Centers for Disease Control and Prevention) 5

6 OpenStax-CNX module: m Figure 4: In this image, the cervical cells on the left are normal and those on the right show enlarged nuclei and hyperchromasia (darkly stained nuclei) typical of HPV-infected koilocytes. (credit: modication of work by Ed Uthman) Most HPV infections resolve spontaneously; however, various therapies are used to treat and remove warts. Topical medications such as imiquimod (which stimulates the production of interferon), podolox, or sinecatechins, may be eective. Warts can also be removed using cryotherapy or surgery, but these approaches are less eective for genital warts than for other types of warts. Electrocauterization and carbon dioxide laser therapy are also used for wart removal. Regular Pap testing can detect abnormal cells that might progress to cervical cancer, followed by biopsy and appropriate treatment. Vaccines for some of the high risk HPV types are now available. Gardasil vaccine includes types 6, 11, 16 and 18 (types 6 and 11 are associated with 90% of genital wart infections and types 16 and 18 are associated with 70% of cervical cancers). Gardasil 9 vaccinates against the previous four types and an additional ve high-risk types (31, 33, 45, 52, and 58). Cervarix vaccine includes just HPV types 16 and 18. Vaccination is the most eective way to prevent infection with oncogenic HPV, but it is important to note that not all oncogenic HPV types are covered by the available vaccines. It is recommended for both boys and girls prior to sexual activity (usually between the ages of nine and fteen).

7 OpenStax-CNX module: m note: Watch a video 4 of how perceptions of HPV aect vaccination rates. note: Few people who have an STI (or think they may have one) are eager to share that information publicly. In fact, many patients are even uncomfortable discussing the symptoms privately with their doctors. Unfortunately, the social stigma associated with STIs makes it harder for infected individuals to seek the treatment they need and creates the false perception that STIs are rare. In reality, STIs are quite common, but it is dicult to determine exactly how common. A recent study on the eects of HPV vaccination found a baseline HPV prevalence of 26.8% for women between the ages of 14 and 59. Among women aged 2024, the prevalence was 44.8%; in other words, almost half of the women in this age bracket had a current infection. 5 According to the CDC, HSV-2 infection was estimated to have a prevalence of 15.5% in younger individuals (1449 years of age) in , down from 20.3% in the same age group in However, the CDC estimates that 87.4% of infected individuals in this age group have not been diagnosed by a physician. 6 Another complicating factor is that many STIs can be asymptomatic or have long periods of latency. For example, the CDC estimates that among women ages 1449 in the United States, about 2.3 million (3.1%) are infected with the sexually transmitted protozoan Trichomonas (see Protozoan Infections of the Urogenital System); however, in a study of infected women, 85% of those diagnosed with the infection were asymptomatic. 7 Even when patients are treated for symptomatic STIs, it can be dicult to obtain accurate data on the number of cases. Whereas STIs like chlamydia, gonorrhea, and syphilis are notiable diseases meaning each diagnosis must be reported by healthcare providers to the CDCother STIs are not notiable (e.g., genital herpes, genital warts, and trichomoniasis). Between the social taboos, the inconsistency of symptoms, and the lack of mandatory reporting, it can be dicult to estimate the true prevalence of STIsbut it is safe to say they are much more prevalent than most people think Eileen F. Dunne, Elizabeth R. Unger, Maya Sternberg, Geraldine McQuillan, David C. Swan, Sonya S. Patel, and Lauri E. Markowitz. Prevalence of HPV Infection Among Females in the United States. Journal of the American Medical Association 297, no. 8 (2007): Centers for Disease Control and Prevention. Genital Herpes - CDC Fact Sheet, Centers for Disease Control and Prevention. Trichomoniasis Statistics,